Yang Gui-Fang, Deng Chang-Sheng, Xiong Yong-Yan, Gong Ling-Ling, Wang Bi-Cheng, Luo Jun
Department of Pathology, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, China.
World J Gastroenterol. 2004 Feb 15;10(4):491-6. doi: 10.3748/wjg.v10.i4.491.
To examine the expression of nuclear factor kappaB (NF-kappaB) and its target genes in intestinal metaplasia (IM), dysplasia (DYS) and gastric carcinoma (GC) infected with Helicobacter pylori (H pylori) and to investigate the mechanism underlying H pylori cytotoxin associated gene A (cag A) infection leading to gastric adenocarcinoma.
Expressions of NF-kappaB/p65 and its target genes: c-myc, cyclinD1 and bcl-xl were immunohistochemically examined in 289 cases of gastric biopsy and resection specimens from patients with IM, DYS and GC infected with H pylori. H pylori in the above mentioned tissues was detected by Warthin-Starry stain and rapid urease tests. IgG antibody to cagA in sera of the patients was measured by ELISA.
The positive rates of NF-kappaB/p65 were significantly higher in groups with cagA of IMI-II(28/33), IM III(48/52), DYSI(27/31), DYS II-III(28/32), GC(35/40) than in groups without cagA of IMI-II(4/17), IMIII(3/20), DYSI(3/20), DYSII-III(6/21), GC(10/23). The expressions of c-myc, cyclinD1, and bcl-xl were significantly higher in groups with cagA of IM III(47/52, 49/52, 46/52), DYSII-III(29/32, 26/32, 25/32) than in groups without cagA of IM III(8/20, 7/20, 5/20), DYSII-III(10/21, 8/21, 3/21), which were in conformity with the expression of NF-kappaB in IM III, and DYSII-III. A significantly higher expression level of NF-kappaB/p65, c-myc, cyclinD1 and bcl-xl was detected in intestinal type GC(27/28, 18/28, 22/28, 24/28) than in diffuse type GC(8/12, 3/12, 3/12, 6/12), respectively.
There may be two different molecular mechanisms in the occurrence of intestinal and diffuse type gastric carcinomas. Intestinal type gastric carcinoma is strongly associated with high expression of c-myc, cyclinD1 and bcl-xl through NF-kappaB/p65 activated by H pylori cagA. Inhibiting the activity of NF-kappaB is an effective and promising way to prevent intestinal type gastric carcinoma.
检测幽门螺杆菌（H pylori）感染的肠化生（IM）、异型增生（DYS）及胃癌（GC）组织中核因子κB（NF-κB）及其靶基因的表达，探讨幽门螺杆菌细胞毒素相关基因A（cag A）感染致胃腺癌的机制。
采用免疫组织化学法检测289例H pylori感染的IM、DYS及GC患者胃活检及手术切除标本中NF-κB/p65及其靶基因c-myc、细胞周期蛋白D1（cyclinD1）和bcl-xl的表达。采用Warthin-Starry染色及快速尿素酶试验检测上述组织中的H pylori。采用酶联免疫吸附测定法检测患者血清中抗cagA IgG抗体。
cagA阳性的IM I-II（28/33）、IM III（48/52）、DYSI（27/31）、DYS II-III（28/32）、GC（35/40）组中NF-κB/p65阳性率显著高于cagA阴性的IM I-II（4/17）、IMIII（3/20）、DYSI（3/20）、DYSII-III（6/21）、GC（10/23）组。cagA阳性的IM III（47/52、49/52、46/52）、DYSII-III（29/32、26/32、25/32）组中c-myc、cyclinD1及bcl-xl的表达显著高于cagA阴性的IM III（8/20、7/20、5/20）、DYSII-III（10/21、8/21、3/21）组，与IM III及DYSII-III中NF-κB的表达一致。肠型GC（27/28、18/28、22/28、24/28）中NF-κB/p65、c-myc、cyclinD1及bcl-xl的表达水平分别显著高于弥漫型GC（8/12、3/12、3/12、6/12）。
肠型和弥漫型胃癌的发生可能存在两种不同的分子机制。肠型胃癌与幽门螺杆菌cagA激活的NF-κB/p65导致c-myc、cyclinD1及bcl-xl高表达密切相关。抑制NF-κB的活性是预防肠型胃癌的有效且有前景的方法。
